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The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells

  • Authors:
    • Ji-Hong Moon
    • Jeong-Min Hong
    • Sang-Youel Park
  • View Affiliations / Copyright

    Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea
    Copyright: © Moon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 430
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    Published online on: April 7, 2021
       https://doi.org/10.3892/mmr.2021.12069
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Abstract

Prion diseases, which involve the alteration of cellular prion protein into a misfolded isoform, disrupt the central nervous systems of humans and animals alike. Prior research has suggested that peroxisome proliferator‑activator receptor (PPAR)γ and autophagy provide some protection against neurodegeneration. PPARs are critical to lipid metabolism regulation and autophagy is one of the main cellular mechanisms by which cell function and homeostasis is maintained. The present study examined the effect of troglitazone, a PPARγ agonist, on autophagy flux in a prion peptide (PrP) (106‑126)‑mediated neurodegeneration model. Western blot analysis confirmed that treatment with troglitazone increased LC3‑II and p62 protein expression, whereas an excessive increase in autophagosomes was verified by transmission electron microscopy. Troglitazone weakened PrP (106‑126)‑mediated neurotoxicity via PPARγ activation and autophagy flux inhibition. A PPARγ antagonist blocked PPARγ activation as well as the neuroprotective effects induced by troglitazone treatment, indicating that PPARγ deactivation impaired troglitazone‑mediated protective effects. In conclusion, the present study demonstrated that troglitazone protected primary neuronal cells against PrP (106‑126)‑induced neuronal cell death by inhibiting autophagic flux and activating PPARγ signals. These results suggested that troglitazone may be a useful therapeutic agent for the treatment of neurodegenerative disorders and prion diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Moon J, Hong J and Park S: The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells. Mol Med Rep 23: 430, 2021.
APA
Moon, J., Hong, J., & Park, S. (2021). The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells. Molecular Medicine Reports, 23, 430. https://doi.org/10.3892/mmr.2021.12069
MLA
Moon, J., Hong, J., Park, S."The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells". Molecular Medicine Reports 23.6 (2021): 430.
Chicago
Moon, J., Hong, J., Park, S."The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells". Molecular Medicine Reports 23, no. 6 (2021): 430. https://doi.org/10.3892/mmr.2021.12069
Copy and paste a formatted citation
x
Spandidos Publications style
Moon J, Hong J and Park S: The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells. Mol Med Rep 23: 430, 2021.
APA
Moon, J., Hong, J., & Park, S. (2021). The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells. Molecular Medicine Reports, 23, 430. https://doi.org/10.3892/mmr.2021.12069
MLA
Moon, J., Hong, J., Park, S."The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells". Molecular Medicine Reports 23.6 (2021): 430.
Chicago
Moon, J., Hong, J., Park, S."The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells". Molecular Medicine Reports 23, no. 6 (2021): 430. https://doi.org/10.3892/mmr.2021.12069
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